Antimicrobial aerosols

Direct Exposure In the event that an individual is at the scene of a known or suspected attack (e.g., white-powder letter, aerosol release, etc.), have them wash their hands and face thoroughly with antimicrobial soap and water as soon as possible. If antimicrobial soap is not available, use any available soap or shampoo. They should also blow their nose to remove any agent particles that may have been captured by nasal mucous. Remove all clothing and seal in a plastic bag. To avoid further exposure of the head, neck, and face to the agent, cut off potentially contaminated clothing that must be pulled over the head. Shower using copious amounts of antimicrobial soap (if available) and water. Ensure that the hair has been washed and rinsed to remove potentially trapped agent. The Centers for Disease Control and Prevention (CDC) does not recommend that individuals use bleach or other disinfectants on their skin. 

Due to the potential for spores to persist after an aerosol exposure, antimicrobial therapy should be continued for 60 days... 

Since the solubility of dimethyl ether in water is about 35%, it can be used to good effect in aqueous aerosol products. It also has antimicrobial effects that are organism-dependent. ... 

The magnitude and duration of drug concentrations above MIC in respiratory secretions after aerosol administration indicate that mhalation therapy may be a suitable option for some bacterial infections of the lower respiratory tract. Pretreatment with a short-acting, aerosolized bronchodilator, such as albuterol sulfate, may improve the pulmonary distribution of aerosolized antimicrobial drugs. 

Aerosol administration of antimicrobial drugs is technically feasible in horses and the available devices can readily deliver clinically relevant dosages to the lower respiratory tract. Controlled, prospective studies must be performed to determine appropriate indications in horses, including the need for concurrent systemic antimicrobial therapy, ideal drug concentrations and dosages and the susceptibility of specific respiratory pathogens. 

Continued antimicrobial prophylaxis for inhalational anthrax for 60 days if aerosol exposure to B. anthrads is known or suspected (2). 

Initial therapy may be altered based on cUnical course of the patient one or two antimicrobial agents (e.g., ciprofloxadn or doxycycline) may be adequate as the patient improves Because of the potential persistence of spores after an aerosol exposure, antimicrobial therapy should be continued for 60 days... 

Part Three is the most extensively modified in the second edition. In the early 1990s asthma was the only disease that was being treated systematically with aerosols. Throughout the decade the concept of treating diabetes with insulin aerosols, cystic fibrosis by gene transfection, and infectious diseases with antimicrobials gained ground. Many of these approaches have yet to be commercial or therapeutic success stories, but by the time this book is in print they may be available to the clinician. Consequently, sections on these topics have been added. 

The Application of Aerosolized Antimicrobial Therapies in Lung Infections... 

The term concentrate or concentrate product has been defined as all of the components that are included in the aerosol formulation with the exception of the propellant [6-8]. The concentrate would, therefore, include the active ingredient, surfactant, solvent, and any additional materials, such as antioxidants or antimicrobials. It may also include low-vapor-pressure propellants such as propellant 11 or cosolvents such as ethanol. 

The inhalation of antimicrobial agents to treat infections in the lung has been of interest for decades [1], As early as the 1950s, extemporaneously prepared antimicrobial agents were aerosolized to treat pneumonia. These preparations were often crude and not well tolerated by patients. Dosage, formulation procedures, and stability assessment in these early reports were not consistent. Although some successes were reported, the potential benefit of this route of administration was not fully appreciated until the 1980s. 

A number of antibiotics have been used as aerosol therapies. Examples include beta lactam agents, polymycin antimicrobials, neomycin, gentamicin, and tobramycin. Many of the early efforts were reported as case studies, and observations and data regarding safety and efficacy were lacking. Controlled clinical trials were not conducted until the middle of the 1980s. More recent evaluations have focused on the role of inhaled tobramycin used as suppressive therapy for cystic fibrosis patients colonized with Pseudomonas aeruginosa. 

Currently, there is a paucity of antimicrobial products delivered by aerosolization. Pentamidine and tobramycin are the only two agents approved for use in the United States as aerosolized antimicrobial therapies. However, interest in using the lung as a site of delivery of therapeutic agents has continued to evolve, and several therapies are under investigation for both local and systemic effects [2],... 

Although antimicrobial therapies have been delivered by aerosolization for over five decades, much is still unknown or not well understood. For example, there are few data to help guide dosing of these therapies. For optimal benefit, an understanding of the clinical utility, as well as the physiologic, physical, chemical, and delivery considerations is essential [6]. 

The potential benefit of aerosolized antibiotic therapy is dependent on three factors characteristics of the disease, aerosol delivery system, and properties of the antimicrobial agent [5]. Diseases that are likely to respond better cause infection in the airway without significant parenchymal or systemic involvement (e.g., cystic fibrosis). There is a significant need for research and scientific advances in the area of aerosol delivery of these therapies. Delivery systems that produce reliable, consistent, and reproducible aerosols are essential. Formulation of drug products requires attention to integrity, stability, tolerability, and overall suitability for aerosolization. 

In addition to these various characteristics, patient-specific factors can affect delivery of aerosolized antimicrobials to the lung. Patient breathing technique and several physiologic variables affect ultimate deposition, including age, breathing pattern, ventilation volumes, and the presence of disease [9]. 

Initial trials of aerosolized antimicrobial therapy with penicillin were published six decades ago [14]. Sporadic reports about the benefit of these therapies continued to appear for the next 30 years as case reports or uncontrolled observations. 

SAFETY CONSIDERATIONS WITH AEROSOLIZED ANTIMICROBIAL THERAPY... 

Generally, aerosol administration of antimicrobial therapies is considered safe however, respiratory and nonrespiratory side effects occur frequently. Some patients experience bronchoconstriction associated with administration. This has been reported when the parenteral form of gentamicin and tobramycin was aerosolized, and may be attributed to other components of the products, including preservatives [29,30]. Cutaneous rashes have developed rarely, and a sore throat may occur. 

The use of antimicrobial therapies through aerosolization avoids many of the toxicities associated with systemic therapy with aminoglycosides or polypeptide agents. However, the risk for promoting antibiotic resistance is a concern. The emergence of highly resistant organisms has been reported... 

Historically, nebulized drug therapy has focused on the administration of bronchodilator therapy. These treatments were often titrated to effect thus, differences in qualitative and quantitative performance between nebulizers were not considered. The administration of aerosolized antimicrobial therapy, as well as other biotechnologic agents, requires greater precision and consistency in delivery. 

Jet and ultrasonic nebulizers have been used to aerosolize antimicrobial therapy. Jet nebulizers used compressed air or oxygen passed through a liquid to produce an aerosol gas. With ultrasonic devices, a piezoelectric element vibrates to generate small aerosol particles. Both systems have advantages and limitations related to their components and technique of use. These are discussed in more detail elsewhere in this text (see Chs. 8, 12). 

Initial experiences with aerosolized antimicrobial therapies appeared in the literature more than 50 years ago. Until the early 1990s, the quality of the evidence supporting this strategy in the management of lung infections was poor. Recently, results from well-controlled clinical trials have established a role for inhaled antibiotics, particularly aminoglycosides, as suppressive therapy for patients with cystic fibrosis. Cyclic therapy with inhaled tobramycin reduces the frequency of pulmonary exacerbations and improves lung function. 

Brucella are facultative intracellular gram-negative bacilli. Humans are infected by this organism after ingesting infected unpasteurized milk or undercooked meat, inhalation of infectious aerosols, or contact with infected tissues. This type of IE is more common in veterinarians and livestock handlers. Cure requires valve replacement and antimicrobial agents including doxycycline with streptomycin or gentamicin or doxycycline with trimethoprim-sulfamethoxazole or rifampin for an extended period (8 weeks to months)." ... 

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